Hydrogel composition and methods for making the same

ABSTRACT

The invention provides a hydrogel composition comprising water and a hydrophilic polymer, wherein the hydrogel composition has (a) an ultimate tensile strength of about 10 kPa or more, (b) a compressive strength of about 70 kPa or more, or (c) an ultimate tensile strength of about 10 kPa or more and a compressive strength of about 70 kPa or more. The invention further provides methods for producing a hydrogel composition.

FIELD OF THE INVENTION

This invention pertains to a hydrogel composition, as well as methodsfor making the same.

BACKGROUND OF THE INVENTION

A “gel” can be defined as a colloid which is in a form that is moresolid than a sol. A “hydrogel” is a gel in which the liquid ordispersion medium is water. Hydrogels can be formed from virtually anysubstance that is capable of forming stable colloids with water. Forexample, silica hydrogels are well known and have been utilized in manyapplications. Hydrogels also can be formed from polymeric substances,such as hydrophilic monomers or polymers.

One of the most common methods for producing hydrogels from hydrophilicmonomers or polymers utilizes an aqueous solution of the hydrophilicmonomer or polymer. In particular, the process begins with thepreparation of a dilute aqueous solution of the hydrophilic monomer orpolymer. The dilute solution is then irradiated or otherwise treated(e.g., with a chemical crosslinking agent) in order to form cross-linksbetween the individual monomer or polymer molecules present in thesolution. As more and more crosslinks are formed between the molecules,the hydrophilic monomer or polymer begins to form a network of polymermolecules that grows until the aqueous solution gels. The resultinghydrogel contains a three dimensional matrix of cross-linked polymermolecules in which the water from the aqueous solution is encapsulated.

Hydrogels made by the aforementioned process are used in manyapplications. However, the limitations inherent in the process impactthe properties of the hydrogels, which prevents them from being used inmany applications. For example, it is often difficult to produce aninitial aqueous solution of the hydrophilic monomer or polymer having aconcentration high enough to produce a hydrogel having an extensivematrix of crosslinked polymer molecules and any significant mechanicalstrength (e.g., compressive strength and/or tensile strength). Indeed,the extent of the polymer network and mechanical properties of thehydrogel can suffer even more when the hydrogel is made from medium tohigh-molecular weight hydrophilic polymers, which tend to haverelatively low water solubilities that prevent the use of aqueousdispersions containing any significant amount of the hydrophilicpolymer. The relatively weak mechanical properties exhibited byhydrogels made by this process severely hamper the usefulness of suchhydrogels in applications that may subject the hydrogel to even moderatemechanical stresses, such as tensile and/or compressive stresses.

Furthermore, insofar as the process requires a uniform aqueous solutionof the hydrophilic monomer or polymer, it is difficult to produce ahydrogel that also contains a water-insoluble material, such as apolymer, uniformly dispersed in the hydrogel. More specifically, it isoften difficult to maintain a uniform dispersion of the water-insolublematerial in the initial aqueous solution of the hydrophilic monomer orpolymer such that the water-insoluble material is uniformly distributedin the hydrogel after the monomer or polymer is crosslinked to producethe hydrogel. Utilizing the aforementioned process, it is also oftendifficult to control the final water content of the hydrogels producedby the process. In particular, the final water content of hydrogelsproduced by the aforementioned process is largely determined by thechemical composition of the hydrogel (i.e., the hydrophilic polymer usedto make the hydrogel) and the degree to which the hydrophilic polymermolecules are cross-linked. Therefore, the amount of water contained inthe hydrogel will be determined, at least in part, by the particularhydrophilic polymer used to make the hydrogel as well as the degree ofcross-linking required to produce a hydrogel having the desiredcharacteristics, and not solely by the desired final water content ofthe hydrogel.

A need therefore remains for hydrogel compositions exhibiting enhancedmechanical properties relative to hydrogel compositions produced bytypical methods. A need also remains for methods of making such hydrogelcompositions exhibiting enhanced mechanical properties. The inventionprovides such a hydrogel composition and methods for making the same.These and other advantages of the invention, as well as additionalinventive features, will be apparent from the description of theinvention provided herein.

BRIEF SUMMARY OF THE INVENTION

The invention provides a hydrogel composition comprising water and ahydrophilic polymer, wherein the hydrogel composition has (a) anultimate tensile strength of about 10 kPa or more, (b) a compressivestrength of about 70 kPa or more, or (c) an ultimate tensile strength ofabout 10 kPa or more and a compressive strength of about 70 kPa or more.

The invention further provides a method for producing a hydrogelcomposition, the method comprising the steps of: (a) providing acompression mold having an internal volume, (b) providing a hydrogelprecursor comprising a melt-processable, radiation crosslinkable,hydrophilic polymer, (c) filling at least a portion of the internalvolume of the compression mold with the precursor, (d) compressing theprecursor contained within the compression mold for a time and underconditions sufficient to form a molded body therefrom, (e) irradiatingat least a portion of the molded body for a time and under conditionssufficient to crosslink at least a portion of the hydrophilic polymercontained within the molded body, and (f) hydrating the irradiatedmolded body for a time and under conditions sufficient to form ahydrogel therefrom.

The invention further provides another method for producing a hydrogelcomposition, the method comprising the steps of: (a) providing adispersion of a crosslinking agent, (b) providing a hydrogel precursorcomprising a melt-processable, hydrophilic polymer, (c) coating at leasta portion of the hydrogel precursor with the dispersion, (d) providing acompression mold having an internal volume, (e) filling at least aportion of the internal volume of the compression mold with the coatedprecursor produced in step (c), (f) compressing the precursor containedwithin the compression mold for a time and under conditions sufficientto form a molded body therefrom and crosslink at least a portion of thehydrophilic polymer contained within the molded body, and (g) hydratingthe molded body for a time and under conditions sufficient to form ahydrogel therefrom.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides a hydrogel composition comprising water and ahydrophilic polymer. The hydrogel composition has (a) an ultimatetensile strength of about 10 kPa or more, (b) a compressive strength ofabout 70 kPa or more, or (c) an ultimate tensile strength of about 10kPa or more and a compressive strength of about 70 kPa or more.

The hydrogel composition of the invention comprises water. Preferably,the water is purified in some manner, such as de-ionization or reverseosmosis. The hydrogel composition of the invention can have any suitablewater content. Preferably, the hydrogel composition of the invention hasa water content of at least about 30% (e.g., at least about 35% or atleast about 38%) more preferably at least about 50%, even morepreferably at least about 75%, even more preferably at least about 90%,and most preferably about 92% to about 95%, based on the total weight ofthe hydrogel composition.

The hydrogel composition of the invention comprises a hydrophilicpolymer. The hydrophilic polymer can be any suitable hydrophilicpolymer, but hydrophilic polymers having a medium to high molecularweight are preferred. In particular, the hydrophilic polymer preferablyhas an average molecular weight of about 400,000 atomic mass units ormore, more preferably about 500,000 atomic mass units or more, and mostpreferably about 1,000,000 atomic mass units or more (e.g., about2,000,000 atomic mass units or more, about 3,000,000 atomic mass unitsor more, about 4,000,000 atomic mass units or more, or even about7,000,000 atomic mass units or more).

Preferably, the hydrophilic polymer is a melt-processable, hydrophilicpolymer, more preferably a melt-processable, radiation crosslinkable,hydrophilic polymer. As utilized herein, the term “melt-processable”refers to a polymer that can be processed in its molten state usingprocesses such as injection molding, extrusion, blow molding, and/orcompression molding. Preferably, a melt processable polymer does notexhibit significant oxidative degradation, decomposition, or pyrolysisat the processing temperatures typically used in such molding processes.The term “radiation crosslinkable,” as utilized herein, refers to apolymer that forms crosslinks between individual polymer molecules whenthe polymer is exposed to a suitable amount of radiation, such as gamma,x-ray, or electron beam radiation. A radiation crosslinkable polymerpreferably does not exhibit significant degradation or chain scissionwhen the polymer is irradiated. In a preferred embodiment, thehydrophilic polymer is poly(ethylene oxide).

The hydrogel composition of the invention can have an ultimate tensilestrength of about 10 kPa or more. As utilized herein, the term “ultimatetensile strength” refers to the maximum resistance to fracture of amaterial (e.g., the hydrogel composition) under tensile stress. Theultimate tensile strength can be measured in accordance with theprocedures outlined in ASTM Standard D638-03 (Type V) and is consideredto be within the ranges set forth herein when so determined by any ofthe procedures in ASTM Standard D638-03 (Type V). In a preferredembodiment, the hydrogel composition of the invention has an ultimatetensile strength of about 20 kPa or more. In a more preferredembodiment, the hydrogel composition of the invention has an ultimatetensile strength of about 30 kPa or more, most preferably about 35 kPaor more (e.g., about 45 kPa or more, or about 50 kPa or more).

The hydrogel composition of the invention can have a compressivestrength of about 70 kPa or more. As utilized herein, the term“compressive strength” refers to the maximum resistance to fracture of amaterial (e.g., the hydrogel composition) under compressive stress. Thecompressive strength of the hydrogel composition can be measured usingany suitable technique. One suitable technique for determining thecompressive strength of a hydrogel is the method of C.Tranquilan-Aranilla et al., which is described in the article“Kappa-carrageenan-polyethylene oxide hydrogel blends prepared by gammairradiation,” Radiation Physics and Chemistry 55:127-131 (1999).Preferably, the compressive strength of the hydrogel composition isdetermined using a modified version of the technique developed by C.Tranquilan-Aranilla et al. in which the sample used for the test ischanged to measure approximately 15.9 mm (0.625 inches) in diameter andabout 6.4 mm (0.25 inches) in thickness. The crosshead speed used in themodified technique is approximately 10 mm/min (0.4 inches/min), which isthe same crosshead speed used by C. Tranquilan-Aranilla et al. Thecompressive strength of a hydrogel is considered to be within the rangesset forth herein when determined using the aforementioned preferredtechnique (i.e., the modified technique based upon the method of C.Tranquilan-Aranilla et al.). In a preferred embodiment, the hydrogelcomposition of the invention has a compressive strength of about 100 kPaor more. In a more preferred embodiment, the hydrogel composition of theinvention has a compressive strength of about 200 kPa or more, mostpreferably about 300 kPa or more (e.g., about 400 kPa or more, about 440kPa or more, about 500 kPa or more, about 600 kPa or more, or about 620kPa or more).

The hydrogel composition of the invention has an ultimate tensilestrength falling within one of the ranges set forth above, a compressivestrength falling within one of the ranges set forth above, or acombination of both an ultimate tensile strength falling within one ofthe ranges set forth above and a compressive strength falling within oneof the ranges set forth above. Preferably, the hydrogel composition ofthe invention has both an ultimate tensile strength falling within oneof the ranges set forth above and a compressive strength falling withinone of the ranges set forth above. For example, in a preferredembodiment, the hydrogel composition of the invention has an ultimatetensile strength of about 10 kPa or more and a compressive strength ofabout 70 kPa or more. In a particularly preferred embodiment, thehydrogel composition of the invention has an ultimate tensile strengthof about 35 kPa or more (e.g., about 45 kPa or more, or about 50 kPa ormore) and a compressive strength of about 300 kPa or more (e.g., about400 kPa or more, or about 440 kPa or more).

The hydrogel composition of the invention can further comprise a secondpolymer in addition to the hydrophilic polymer. The second polymer canbe any suitable polymer, such as a hydrophilic polymer or a hydrophobicor water-insoluble polymer. Hydrophilic polymers suitable for use as thesecond polymer include, but are not limited to, polyethylene glycol,polyethylene glycol copolymers (e.g., poly(ethylene glycol-co-propyleneglycol) copolymers, poly(ethylene glycol)-poly(propyleneglycol)-poly(ethylene glycol) block copolymers, or poly(propyleneglycol)-poly(ethylene glycol)-poly(propylene glycol) block copolymers),poly(propylene glycol), poly(2-hydroxyethyl methacrylate), poly(vinylalcohol), poly(acrylic acid), poly(methacrylic acid),polyvinylpyrrolidone, cellulose ether, alginate, chitosan, hyaluronate,collagen, and mixtures or combinations thereof. Alternatively, thesecond polymer can be an absorbable polymer (i.e., a polymer whichdegrades in vivo into non-toxic substances that can be eliminated by thebody). Absorbable polymers suitable for use as the second polymerinclude, but are not limited to, polylactic acid, polyglycolic acid,polydioxanone, polycaprolactone, beta-hydroxy acid polymers, andcombinations thereof.

The hydrogel composition of the invention also can contain any suitableactive ingredient, such as a drug (e.g., lidocaine), a therapeuticagent, or a humectant. The active ingredients can be incorporated in thehydrogel composition by any suitable means. For example, the activeingredient can be incorporated (e.g., dry blended) into the precursorutilized to produce the hydrogen composition. Alternatively, the activeingredient can be incorporated into the hydrogel composition during thehydration process. In particular, the hydrogel precursor can be hydratedutilizing an aqueous solution containing the active ingredient.Alternatively, a hydrogel composition according to the invention can bedehydrated or dried to produce a xerogel, and then the xerogel can behydrated utilizing an aqueous solution containing the active ingredient.

The hydrogel composition of the invention is well suited for manyapplications, especially those applications requiring hydrogels capableof withstanding moderate to high mechanical stresses without failing.For example, the hydrogel composition of the invention is well suitedfor use in many biomedical applications. Suitable biomedicalapplications include, but are not limited to, anti-adhesion barriers(e.g., a barrier that prevents the abnormal adhesion of collagen fibersto structures during immobilization following trauma or surgery),contact lenses, drug delivery devices, prosthetic nuclear discs, wounddressings, and soft tissue repair structures (e.g., artificialcartilage).

The invention also provides methods for producing a hydrogelcomposition. In a first embodiment, the invention provides a method forproducing a hydrogel composition, the method comprising the steps of (a)providing a compression mold having an internal volume, (b) providing ahydrogel precursor comprising a melt-processable, radiationcrosslinkable, hydrophilic polymer, (c) filling at least a portion ofthe internal volume of the compression mold with the precursor, (d)compressing the precursor contained within the compression mold for atime and under conditions sufficient to form a molded body therefrom,(e) irradiating at least a portion of the molded body for a time andunder conditions sufficient to crosslink at least a portion of thehydrophilic polymer contained within the molded body, and (f) hydratingthe irradiated molded body for a time and under conditions sufficient toform a hydrogel therefrom.

The hydrogel precursor utilized in this first method embodiment of theinvention comprises a melt-processable, radiation-crosslinkable,hydrophilic polymer. The melt-processable, radiation-crosslinkable,hydrophilic polymer contained in the hydrogel precursor can be anysuitable polymer, but hydrophilic polymers having a medium to highweight average molecular weight are preferred. In particular, thehydrophilic polymer preferably has an average molecular weight of about400,000 atomic mass units or more, more preferably about 500,000 atomicmass units or more, and most preferably about 1,000,000 atomic massunits or more (e.g., about 2,000,000 atomic mass units or more, about3,000,000 atomic mass units or more, or even about 4,000,000 atomic massunits or more). In a preferred embodiment, the hydrophilic polymer ispoly(ethylene oxide).

The molded body produced during the compression step of this methodembodiment of the invention can be irradiated using any suitable method,many of which are known in the art. For example, the molded body can beirradiated by exposing the mass to a suitable amount of gamma, x-ray, orelectron beam radiation. Preferably, the molded body is irradiated byexposing it to about 0.5 Mrad to about 50 Mrad (e.g., about 0.5 Mrad toabout 10 Mrad, or about 1.5 to about 6 Mrad) of gamma radiation. Whilethe molded body can be exposed to amounts of radiation falling outsideof the aforementioned range, such amounts of radiation tend to producehydrogels with unsatisfactory properties. In particular, radiation dosesof less than about 0.5 Mrad generally provide insufficient cross-linkingof the hydrophilic polymer to produce an extensive matrix ofcross-linked polymer molecules and a coherent hydrogel. Furthermore,while doses of greater than 50 Mrad may be used, the additionalimprovement in the extent of cross-linking of the hydrophilic polymerthat is achieved generally is offset by the degradation of thehydrophilic polymer that can occur with such high doses of radiation.

Preferably, the molded body is irradiated in an inert orreduced-pressure atmosphere. Irradiating the molded body in an inert(i.e., non-oxidizing) or reduced-pressure atmosphere reduces the effectsof oxidation and chain scission reactions which can occur duringirradiation in an oxidative atmosphere. Typically, the molded body isplaced in an oxygen-impermeable package during the irradiation step.Suitable oxygen-impermeable packaging materials include, but are notlimited to, aluminum, polyester coated metal foil (e.g., the Mylar®product available from DuPont Teijin Films), polyethylene terephthalate,and poly(ethylene vinyl alcohol). In order to further reduce the amountof oxidation which occurs during the irradiation of the molded body, theoxygen-impermeable packaging may be evacuated (e.g., the pressure withinthe packaging may be reduced below the ambient atmospheric pressure)and/or flushed with an inert gas (e.g., nitrogen, argon, helium, ormixtures thereof) after the molded body has been placed therein.

In a second embodiment, the invention provides a method for producing ahydrogel composition, the method comprising the steps of (a) providing adispersion of a crosslinking agent, (b) providing a hydrogel precursorcomprising a melt-processable, hydrophilic polymer, (c) coating at leasta portion of the hydrogel precursor with the dispersion, (d) providing acompression mold having an internal volume, (e) filling at least aportion of the internal volume of the compression mold with the coatedprecursor produced in step (c), (f) compressing the precursor containedwithin the compression mold for a time and under conditions sufficientto form a molded body therefrom and crosslink at least a portion of thehydrophilic polymer contained within the molded body, and (g) hydratingthe molded body for a time and under conditions sufficient to form ahydrogel therefrom.

The dispersion of the crosslinking agent utilized in this second methodembodiment of the invention can contain any suitable crosslinking agent(e.g., a chemical crosslinking agent) dispersed in any suitable medium.Preferably, the crosslinking agent is a peroxide. Preferred peroxidecrosslinking agents have a decomposition temperature of about 100° C. toabout 125° C., such as benzoyl peroxide. In a preferred embodiment, themedium of the dispersion is an organic solvent, such as ethyl acetate.

The hydrogel precursor utilized in the second method embodiment of theinvention comprises a melt-processable, hydrophilic polymer. Themelt-processable, hydrophilic polymer contained in the hydrogelprecursor can be any suitable polymer, but hydrophilic polymers having amedium to high weight average molecular weight are preferred. Inparticular, the hydrophilic polymer preferably has an average molecularweight of about 400,000 atomic mass units or more, more preferably about500,000 atomic mass units or more, and most preferably about 1,000,000atomic mass units or more (e.g., about 2,000,000 atomic mass units ormore, about 3,000,000 atomic mass units or more, or even about 4,000,000atomic mass units or more). In a preferred embodiment, the hydrophilicpolymer is poly(ethylene oxide).

As noted above, the methods of the invention comprise providing acompression mold for the hydrogel composition having an internal volume.The term “compression mold” is utilized herein to refer to a moldtypically having two halves which, when joined together, define aninternal volume (i.e., mold cavity). The compression mold can beprovided in any suitable configuration. Generally, the compression moldis configured such that the internal volume of the compression mold(i.e., the mold cavity) defines a molded body in a substantiallycomplete form (i.e., in substantially the same form as will be used forthe hydrogel composition). However, it will be understood that themolded body produced in step (d) of the first method embodiment and step(f) of the second method embodiment also can be subjected to furtherprocessing (e.g., machining) to provide the molded body in a form thatwill produce a hydrogel composition having the desired final form.

The hydrogel precursors utilized in the methods of the invention can beprovided in any suitable form. For example, the hydrogel precursor canbe provided in the form of a molten matrix containing the hydrophilicpolymer and any other suitable additives (e.g., second polymer, activeingredient, etc.). Preferably, the hydrogel precursor is provided in aform selected from the group consisting of a powder, pellets, or acombination thereof.

The hydrogel precursors utilized in the methods of the invention canfurther comprise a second polymer in addition to the hydrophilicpolymer. The second polymer can be any suitable polymer, such as ahydrophilic polymer or a hydrophobic or water-insoluble polymer.Hydrophilic polymers suitable for use as the second polymer include, butare not limited to, polyethylene glycol, polyethylene glycol copolymers(e.g., poly(ethylene glycol-co-propylene glycol) copolymers,poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) blockcopolymers, or poly(propylene glycol)-poly(ethyleneglycol)-poly(propylene glycol) block copolymers), poly(propyleneglycol), poly(2-hydroxyethyl methacrylate), poly(vinyl alcohol),poly(acrylic acid), poly(methacrylic acid), polyvinylpyrrolidone,cellulose ether, alginate, chitosan, hyaluronate, collagen, and mixturesor combinations thereof. Alternatively, the second polymer can be anabsorbable polymer (i.e., a polymer which degrades in vivo intonon-toxic substances that can be eliminated by the body). Absorbablepolymers suitable for use as the second polymer include, but are notlimited to, polylactic acid, polyglycolic acid, polydioxanone,polycaprolactone, beta-hydroxy acid polymers, and mixtures orcombinations thereof.

When present in the hydrogel precursor, the optional second polymer canbe incorporated into the hydrogel precursor by any suitable means. Forexample, when the optional second polymer is melt-processable, thesecond polymer can be melted and uniformly dispersed in a molten matrixof the hydrophilic polymer. When the optional second polymer is notmelt-processable, the second polymer can be dry blended with thehydrophilic polymer to produce a polymer blend or mixture prior to thecompression molding step.

The hydrogel precursors utilized in the methods of the invention canalso contain any suitable active ingredient, such as a drug (e.g.,lidocaine), therapeutic agent, or humectant. The active ingredients canbe incorporated in the hydrogel precursor by any suitable means. Forexample, the active ingredient can be incorporated (e.g., dry blended)into the precursor utilized to produce the hydrogel composition.Alternatively, the hydrogel precursor can be coated with the activeingredient, for example, by immersing at least a portion of the hydrogelprecursor in a solution or dispersion containing the active ingredientand subsequently drying the coated precursor to remove the liquidmedium.

As noted above, at least a portion of the internal volume of thecompression mold (i.e., mold cavity) is filled with the hydrogelprecursor. Preferably, the portion of the internal volume of thecompression mold filled with the mixture comprises a portion of asurface layer of the final hydrogel composition. More preferably,substantially all of the internal volume of the compression mold isfilled with the hydrogel precursor. When only a portion of the internalvolume of the compression mold is filled with the hydrogel precursor,the remaining portion of the internal volume of the compression moldpreferably is filled with another melt-processable polymer, such asultrahigh molecular weight polyethylene.

After at least a portion of the internal volume of the compression moldis filled, the hydrogel precursor contained within the compression moldis compressed for a time and under conditions (e.g., pressure andtemperature) sufficient to form a molded body therefrom. It will beunderstood that the hydrogel precursor is compressed by any suitablemeans, such as by mating the two halves of a two-part compression moldand applying an external force in a direction such that any substancecontained within the mold (e.g., the hydrogel precursor) is subjected toa compressive force.

Typically, the precursor is subjected to a pressure of about 3,400 kPato about 28,000 kPa during the compression molding step. Preferably, theprecursor is subjected to a pressure of about 3,800 kPa to about 14,000kPa. During the compression molding step, the precursor typically issubjected to a temperature of about 70° C. to about 200° C. Preferably,the precursor is subjected to a temperature of about 90° C. to about180° C., more preferably a temperature of about 120° C. to about 140°C., during the compression molding step. The hydrogel precursor can becompressed in the compression mold for any amount of time sufficient toform a molded body therefrom. Typically, the precursor is compressed forabout 5 to about 30 minutes, more preferably about 5 to about 10minutes, during the compression molding step. It will also be understoodthat the particular time and conditions (e.g., pressure and temperature)necessary to form a molded body from the hydrogel precursor will dependupon several factors, such as the composition of the hydrogel precursor(e.g., the type and/or amount of melt-processable, hydrophilic polymercontained in the precursor), and the size (e.g., thickness) of thedesired molded body, as well as other factors.

The molded body produced during the inventive methods can be hydrated toform the hydrogel composition using any suitable technique. Typically,at least a portion of the molded body is submerged in an aqueoussolution (e.g., de-ionized water, water filtered via reverse osmosis, asaline solution, or an aqueous solution containing a suitable activeingredient) for an amount of time sufficient to produce a hydrogelcomposition having the desired water content. For example, when ahydrogel composition comprising the maximum water content is desired,the molded body is submerged in the aqueous solution for an amount oftime sufficient to allow the molded body to swell to its maximum size orvolume. Typically, the molded body is submerged in the aqueous solutionfor at least about 50 hours, preferably at least about 100 hours, andmore preferably about 120 hours to about 240 hours (e.g., about 120hours to about 220 hours). It will be understood that the amount of timenecessary to hydrate the molded body to the desired level to form thehydrogel composition will depend upon several factors, such as thecomposition of the hydrogel precursor (e.g., the type and/or amount ofmelt-processable, hydrophilic polymer contained in the precursor), thesize (e.g., thickness) of the molded body, and the temperature of theaqueous solution, as well as other factors. The aqueous solution used tohydrate the molded body can be maintained at any suitable temperature.Typically, the aqueous solution is maintained at a temperature of atleast about 25° C., more preferably at a temperature of about 30° C. toabout 100° C., and most preferably at a temperature of about 40° C. toabout 90° C. (e.g., about 50° C. to about 90° C., or about 50° C. toabout 80° C.).

The methods of the invention can further comprise the step ofsterilizing the hydrogel composition using any suitable process. Thehydrogel composition can be sterilized at any suitable point, butpreferably is sterilized after the molded body/hydrogel precursor ishydrated. Suitable non-irradiative sterilization techniques include, butare not limited to, gas plasma or ethylene oxide methods known in theart. For example, the hydrogel composition can be sterilized using aPlazLyte® Sterilization System (Abtox, Inc., Mundelein, Ill.) or inaccordance with the gas plasma sterilization processes described in U.S.Pat. Nos. 5,413,760 and 5,603,895. In some circumstances, such as whenthe interior portions of the hydrogel composition require sterilization,the hydrogel composition can be sterilized using gamma irradiation at arelatively low dose of approximately 1.5 Mrad to about 4 Mrad usingmethods known in the art.

The hydrogel compositions produced by the methods of the invention canbe packaged in any suitable packaging material. Desirably, the packagingmaterial maintains the sterility of the hydrogel composition until thepackaging material is breached.

EXAMPLE

This example further illustrates the invention but, of course, shouldnot be construed as in any way limiting its scope. This exampledemonstrates the production of a hydrogel composition according to theinvention.

A hydrogel precursor comprising poly(ethylene oxide) having an averagemolecular weight of approximately 7 million atomic mass units (POLYOX™WSR-303 poly(ethylene oxide) (available from The Dow Chemical Company,Midland, Mich.)) was placed into a compression mold having an internalvolume. The internal volume of the compression mold defined a diskmeasuring approximately 89 mm (3.5 inches) in diameter and approximately3.2 mm (0.125 inches) in thickness, and the hydrogel precursorcompletely filled the compression mold. The precursor was packed intothe compression mold by subjecting the precursor to a compressive forceof approximately 2700 kPa (400 psi) for approximately 2-3 minutes atroom temperature. Following the packing step, the temperature within thecompression mold was increased from room temperature to approximately127° C. (260° F.) at a rate of approximately 3.3° C./min (6° F./min)while the pressure on the compression mold was increased from 2700 kPa(400 psi) to about 11,000 kPa (1600 psi). The temperature and pressurewithin the compression mold were then maintained at approximately 127°C. (260° F.) and 11,000 kPa (1600 psi) for approximately 15 minutes.Following the compression step, the resulting molded disk was cooledfrom 127° C. (260° F.) to room temperature (i.e., approximately 22° C.(72° F.)) at rate of approximately 3.9° C./min (7° F./min) while thepressure was reduced from 11,000 kPa (1600 psi) to approximately 480 kPa(70 psi). The above-described process was repeated four times to producea total of five molded disks. Each of the disks was then analyzed todetermine the average mechanical properties of a disk produced by theprocess. The resulting molded disks exhibited an average ultimatetensile strength of approximately 27,650 kPa (4,010 psi), an averageelongation at fracture of approximately 800%, and an average Young'smodulus of approximately 122 MPa (17,700 psi), as determined inaccordance with ASTM Standard D638-03 (Type V).

Five molded disks produced by the above-described process wereseparately vacuum-packaged in aluminum foil bags. The packaged diskswere then irradiated by exposing the disks to approximately 5 Mrad (50kGy) of gamma radiation. Following the irradiation step, the irradiateddisks were maintained in the aluminum foil bags in order to protect thepoly(ethylene oxide) contained in the disks from oxidative degradation.Next, the irradiated disks were removed from the foil bag and submergedin water filtered via reverse osmosis. The molded disks were allowed toremain in the water, which was maintained at room temperature (i.e.,approximately 22° C. (72° F.)), and swell until an equilibrium state wasreached, which typically took approximately 170 hours (7 days). Theresulting hydrogel compositions had an average gel content ofapproximately 74% and an average water content of approximately 92%.

The resulting hydrogel compositions exhibited improved tensile strengthwhen compared to a hydrogel produced by a typical solution-basedprocess. In particular, a hydrogel produced by a typical solution-basedprocess exhibited an ultimate tensile strength that was too low to bemeasured in accordance with the procedures set forth in ASTM StandardD638-03 (Type V). Indeed, the hydrogel sample used in taking themeasurements typically fractured before the sample could be mounted onthe testing apparatus. Conversely, the hydrogel compositions of theinvention exhibited an average ultimate tensile strength ofapproximately 52 kPa (7.6 psi) and an average elongation at fracture ofapproximately 253%, as determined in accordance with ASTM StandardD638-03 (Type V).

The resulting hydrogel compositions also exhibited improved compressivestrength when compared to hydrogels produced by the solution-basedprocess. A hydrogel produced by a typical solution-based processexhibited a maximum compressive strength of approximately 41 kPa (6psi), as determined using the preferred modified technique of C.Tranquilan-Aranilla et al. described above. By way of contrast, thehydrogel compositions of the invention exhibited an average compressivestrength of approximately 630 kPa (92 psi), when measured using the sameprocedure. The hydrogel compositions of the invention also exhibited anelasticity sufficient to allow the hydrogel composition to retain itsoriginal shape after it has been compressed to a height equal toapproximately 50% of its original (i.e., uncompressed) height.

As evidenced by the data set forth above, the hydrogel composition ofthe invention exhibits improved mechanical properties as compared tohydrogels produced by typical processes, such as a solution-basedprocess. In particular, the tensile properties of the hydrogelcomposition of the invention are significantly improved over typicalhydrogels. Also, the compressive strength of the hydrogel composition ofthe invention is over ten times greater than the compressive strength oftypical hydrogels (i.e., hydrogels produced by a typical solution-basedprocess). These improved mechanical properties make the hydrogelcomposition of the invention suitable for applications in which thehydrogel composition may be subjected to moderate mechanical stresses,such as tensile and/or compressive stresses.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference to the sameextent as if each reference were individually and specifically indicatedto be incorporated by reference and were set forth in its entiretyherein.

The use of the terms “a” and “an” and “the” and similar referents in thecontext of describing the invention (especially in the context of thefollowing claims) are to be construed to cover both the singular and theplural, unless otherwise indicated herein or clearly contradicted bycontext. The terms “comprising,” “having,” “including,” and “containing”are to be construed as open-ended terms (i.e., meaning “including, butnot limited to,”) unless otherwise noted. Recitation of ranges of valuesherein are merely intended to serve as a shorthand method of referringindividually to each separate value falling within the range, unlessotherwise indicated herein, and each separate value is incorporated intothe specification as if it were individually recited herein. All methodsdescribed herein can be performed in any suitable order unless otherwiseindicated herein or otherwise clearly contradicted by context. The useof any and all examples, or exemplary language (e.g., “such as”)provided herein, is intended merely to better illuminate the inventionand does not pose a limitation on the scope of the invention unlessotherwise claimed. No language in the specification should be construedas indicating any non-claimed element as essential to the practice ofthe invention.

Preferred embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention.Variations of those preferred embodiments may become apparent to thoseof ordinary skill in the art upon reading the foregoing description. Theinventors expect skilled artisans to employ such variations asappropriate, and the inventors intend for the invention to be practicedotherwise than as specifically described herein. Accordingly, thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

1. A hydrogel composition comprising water and a hydrophilic polymer,wherein the hydrogel composition has (a) an ultimate tensile strength ofabout 10 kPa or more, (b) a compressive strength of about 70 kPa ormore, or (c) an ultimate tensile strength of about 10 kPa or more and acompressive strength of about 70 kPa or more.
 2. The hydrogelcomposition of claims 1, wherein the hydrophilic polymer is amelt-processable, hydrophilic polymer.
 3. The hydrogel composition ofclaim 2, wherein the hydrophilic polymer is a melt-processable,radiation crosslinkable, hydrophilic polymer
 4. The hydrogel compositionof claim 3, wherein the hydrophilic polymer is poly(ethylene oxide). 5.The hydrogel composition of claim 1, wherein the hydrogel compositionhas an ultimate tensile strength of about 35 kPa or more.
 6. Thehydrogel composition of claim 1, wherein the hydrogel composition has acompressive strength of about 300 kPa or more.
 7. The hydrogelcomposition of claim 1, wherein the hydrogel composition furthercomprises a second polymer selected from the group consisting ofpolyethylene glycol, polyethylene glycol copolymers, poly(propyleneglycol), poly(2-hydroxyethyl methacrylate), poly(vinyl alcohol),poly(acrylic acid), poly(methacrylic acid), polyvinylpyrrolidone,cellulose ether, alginate, chitosan, hyaluronate, collagen, polylacticacid, polyglycolic acid, polydioxanone, polycaprolactone, beta-hydroxyacid polymers, and mixtures thereof.
 8. A drug delivery devicecomprising the hydrogel composition of claim 1 and an active ingredientdispersed or dissolved in the hydrogel composition.
 9. A wound dressingcomprising the hydrogel composition of claim
 1. 10. A method forproducing a hydrogel composition, the method comprising the steps of:(a) providing a compression mold having an internal volume, (b)providing a hydrogel precursor comprising a melt-processable, radiationcrosslinkable, hydrophilic polymer, (c) filling at least a portion ofthe internal volume of the compression mold with the precursor, (d)compressing the precursor contained within the compression mold to forma molded body therefrom, (e) irradiating at least a portion of themolded body to crosslink at least a portion of the hydrophilic polymercontained within the molded body, and (f) hydrating the irradiatedmolded body to form a hydrogel therefrom.
 11. The method of claim 10,wherein the melt-processable, radiation crosslinkable, hydrophilicpolymer has an average molecular weight of about 1,000,000 atomic massunits or more.
 12. The method of claim 11, wherein the melt-processable,radiation crosslinkable, hydrophilic polymer is poly(ethylene oxide).13. The method of claim 10, wherein the precursor is compressed at apressure of about 3,800 kPa to about 14,000 kPa during step (d).
 14. Themethod of claim 10, wherein the precursor is heated to a temperature ofabout 120° C. to about 140° C. during step (d).
 15. The method of claim10, wherein the precursor is compressed for about 5 to about 10 minutesduring step (d).
 16. The method of claim 10, wherein the molded body isirradiated in step (e) by exposing the molded body to about 1.5 to about6 Mrad of gamma radiation.
 17. The method of claim 10, wherein themolded body is hydrated by submerging at least a portion of the moldedbody in an aqueous solution having a temperature of about 50° C. toabout 90° C. for about 120 hours to about 220 hours.
 18. The method ofclaim 17, wherein the aqueous solution further comprises an activeingredient selected from the group consisting of a drug, a therapeuticagent, a humectant, and mixtures thereof.
 19. The method of claim 10,wherein the hydrogel precursor further comprises an active ingredientselected from the group consisting of a drug, a therapeutic agent, ahumectant, and mixtures thereof.
 20. A method for producing a hydrogelcomposition, the method comprising the steps of: (a) providing adispersion comprising a crosslinking agent, (b) providing a hydrogelprecursor comprising a melt-processable, hydrophilic polymer, (c)coating at least a portion of the hydrogel precursor with thedispersion, (d) providing a compression mold having an internal volume,(e) filling at least a portion of the internal volume of the compressionmold with the coated precursor produced in step (c), (f) compressing theprecursor contained within the compression mold to form a molded bodytherefrom and crosslink at least a portion of the hydrophilic polymercontained within the molded body, and (g) hydrating the molded body toform a hydrogel therefrom.
 21. The method of claim 20, wherein thecrosslinking agent is a peroxide.
 22. The method of claim 21, whereinthe crosslinking agent is benzoyl peroxide.
 23. The method of claim 20,wherein the melt-processable, hydrophilic polymer has an averagemolecular weight of about 1,000,000 atomic mass units or more.
 24. Themethod of claim 23, wherein the melt-processable, hydrophilic polymer ispoly(ethylene oxide).
 25. The method of claim 20, wherein the precursoris compressed at a pressure of about 3,800 kPa to about 14,000 kPaduring step (f).
 26. The method of claim 20, wherein the precursor isheated to a temperature of about 120° C. to about 140° C. during step(f).
 27. The method of claim 20, wherein the precursor is compressed forabout 5 to about 10 minutes during step (f).
 28. The method of claim 20,wherein the molded body is hydrated by submerging at least a portion ofthe molded body in an aqueous solution having a temperature of about 50°C. to about 90° C. for about 120 hours to about 220 hours.
 29. Themethod of claim 28, wherein the aqueous solution further comprises anactive ingredient selected from the group consisting of a drug, atherapeutic agent, a humectant, and mixtures thereof.
 30. The method ofclaim 20, wherein the hydrogel precursor further comprises an activeingredient selected from the group consisting of a drug, a therapeuticagent, a humectant, and mixtures thereof.